Document Detail

Helicobacter pylori immune escape is mediated by dendritic cell-induced Treg skewing and Th17 suppression in mice.
MedLine Citation:
PMID:  19931266     Owner:  NLM     Status:  MEDLINE    
BACKGROUND & AIMS: Helicobacter pylori infection increases gastric regulatory T cell (Treg) response, which may contribute to H pylori immune escape. We hypothesize that H pylori directs Treg skewing by way of dendritic cells (DCs) and thus inhibits interleukin-17(+) helper T cells (Th17) immunity.
METHODS: Two-photon microscopy was used to locate DCs in gastric lamina propria of mice. The induction of Th17 and Treg responses by bacteria-pulsed murine bone marrow-derived DCs was analyzed by cytokine production and stimulation of T-cell proliferation. The effect of VacA, CagA, transforming growth factor-beta (TGF-beta), and IL-10 on Th17/Treg balance was assessed. The in vivo significance of Tregs on the H pylori-specific Th17 response and H pylori density was determined by using anti-CD25 neutralizing antibodies to deplete Tregs in mice.
RESULTS: We showed that mucosal CD11c(+) DCs are located near the surface of normal gastric epithelium, and their number increased after H pylori infection. Study of the direct interaction of DCs with H pylori showed a Treg-skewed response. The Treg skewing was independent of H pylori VacA and CagA and dependent on TGF-beta and IL-10. In vivo Treg skewing by adoptive transfer of H pylori-pulsed DCs reduces the ratio of gastric IL-17/Foxp3 mRNA expressions. The depletion of CD25(+) Tregs results in early reduction of H pylori density, which is correlated with enhanced peripheral H pylori-specific Th17, but not Th1, response.
CONCLUSIONS: Overall, our study indicates that H pylori alters the DC-polarized Th17/Treg balance toward a Treg-biased response, which suppresses the effective induction of H pylori-specific Th17 immunity.
John Y Kao; Min Zhang; Mark J Miller; Jason C Mills; Baomei Wang; Maochang Liu; Kathyn A Eaton; Weiping Zou; Bradford E Berndt; Tyler S Cole; Tomomi Takeuchi; Stephanie Y Owyang; Jay Luther
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-18
Journal Detail:
Title:  Gastroenterology     Volume:  138     ISSN:  1528-0012     ISO Abbreviation:  Gastroenterology     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-02     Completed Date:  2010-03-25     Revised Date:  2014-09-14    
Medline Journal Info:
Nlm Unique ID:  0374630     Medline TA:  Gastroenterology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1046-54     Citation Subset:  AIM; IM    
Copyright Information:
Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Adoptive Transfer
Antigens, Bacterial / immunology
Bacterial Proteins / immunology
Cell Proliferation
Cells, Cultured
Dendritic Cells / immunology*,  microbiology
Disease Models, Animal
Forkhead Transcription Factors / metabolism
Gastric Mucosa / immunology*,  microbiology
Helicobacter Infections / immunology*,  microbiology
Helicobacter pylori / growth & development,  immunology*
Immune Evasion*
Interleukin-10 / metabolism
Interleukin-17 / immunology*
Interleukin-2 Receptor alpha Subunit / metabolism
Lymphocyte Activation
Mice, Inbred C57BL
Microscopy, Confocal
Microscopy, Fluorescence, Multiphoton
RNA, Messenger / metabolism
T-Lymphocyte Subsets / immunology*,  microbiology
T-Lymphocytes, Regulatory / immunology*
Time Factors
Transforming Growth Factor beta / metabolism
Grant Support
1 KO8 DK0669907-01/DK/NIDDK NIH HHS; K08 DK069907/DK/NIDDK NIH HHS; K08 DK069907-01A1/DK/NIDDK NIH HHS; R01 DK079798/DK/NIDDK NIH HHS; R01 DK079798-01/DK/NIDDK NIH HHS; R01 DK079798-01A2/DK/NIDDK NIH HHS
Reg. No./Substance:
0/Antigens, Bacterial; 0/Bacterial Proteins; 0/Forkhead Transcription Factors; 0/Foxp3 protein, mouse; 0/Il2ra protein, mouse; 0/Interleukin-17; 0/Interleukin-2 Receptor alpha Subunit; 0/RNA, Messenger; 0/Transforming Growth Factor beta; 0/VacA protein, Helicobacter pylori; 0/cagA protein, Helicobacter pylori; 130068-27-8/Interleukin-10

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